Trikafta in Cystic Fibrosis Patients

NCT03506061 | Completed Phase 2 Results DMC FDA Drug

• 3 other identifiers: IRB00108656300001205R01HL139876
• Study Type: interventional
• Target: 42
• Locations: 1 country
• Sites: 2

Brief Summary

This clinical study will enroll 42 participants without the F508del mutation, carrying partial function or N1303K mutations not approved for Trikafta, and who are not expected to be approved for CFTR modulator treatment in the immediate future. Each participant will be given Trikafta for approximately four weeks. The study researchers will monitor clinical endpoints that include forced expiratory volume (FEV1) and sweat chloride. Additionally, the researchers will obtain skin biopsy material and/or blood sample from each subject so that induced pluripotent stem (iPS) cells can be modified into airway cell monolayers and tested for response to Trikafta. In this way, the study will evaluate an emerging and readily accessible in vitro endpoint as a predictor of clinical response. This study will serve as a pilot/test case for other clinical protocols relevant to patients with rare CFTR variants who do not currently receive modulator therapies.

Conditions

Cystic Fibrosis

Outcome Measures

Primary Outcomes (3)

• Percent Predicted Forced Expiratory Volume in One Second (FEV1) Among Participants With Evidence of Partial Function

  FEV1 provides a direct measurement of patient health among individuals with cystic fibrosis and declines in FEV1 are associated with poor outcomes among those with CF. FEV1 is measured by spirometry and is the maximum amount of air the participant can blow out in one second.

  Baseline, Day 28

• Sweat Chloride Among Participants Who Encode the N1303K Variant

  Persons with CF have higher levels of chloride in their sweat. Sweat chloride concentrations of less than or equal to 29 mmol/L are considered normal, concentrations of 30-59 mmol/L are considered intermediate and indicate that the individual may have CF. Concentrations of 60 mmol/L and greater mean that a diagnosis of CF is likely.

  Baseline, Day 28

• Number of Participants With Induced Pluripotent Stem (iPS) Cells Predicting Response to Treatment Among Participants With Evidence of Partial Function

  Response of iPS cells (iPSc) to treatment among participants with evidence of partial function was examined to determine whether iPS derived monolayers could predict "personalized" clinical benefit. Cutaneous punch biopsy material was collected from each participant so that iPS cells could be differentiated into airway epithelial monolayers and tested for response to treatment in vitro - as a potential way to predict improvement from Trikafta in vivo.

  Baseline

Secondary Outcomes (6)

• Percent Predicted Forced Expiratory Volume in One Second (FEV1) Among Participants Who Encode the N1303K Variant

  Baseline, Day 28

• Sweat Chloride Among Participants With Evidence of Partial Function

  Baseline, Day 28

• Cystic Fibrosis Questionnaire - Revised (CFQ-R) Respiratory Domain Score

  Baseline, Day 28

• Weight

  Baseline, Day 28

• Body Mass Index (BMI)

  Baseline, Day 28

Study Arms (2)

Substudy 1 - Participants With Evidence of Partial Function

EXPERIMENTAL

Participants with CF with evidence of partial function (sweat chloride \< 80 milliequivalents per liter (mEq/L) or pancreatic sufficiency) will receive Trikafta for 28 days.

Drug: Trikafta

Substudy 2 - Participants who Encode the N1303K Variant

EXPERIMENTAL

Participants with CF who encode the N1303K variant will receive Trikafta for 28 days.

Drug: Trikafta

Interventions

Trikafta DRUG

Participants will take Trikafta which is a combination tablet comprised of 100 milligrams (mg) of elexacaftor, 50 mg of tezacaftor and 75 mg of ivacaftor (2 tablets taken in the morning), and 150 mg of ivacaftor taken in the evening.

Also known as: ivacaftor, tezacaftor, elexacaftor

Substudy 1 - Participants With Evidence of Partial Function; Substudy 2 - Participants who Encode the N1303K Variant

Eligibility Criteria

• Age: 12 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Provision of signed and dated informed consent form or assent form
• Stated willingness to comply with all study procedures and availability for the duration of the study
• Male or female age ≥12
• A clinical diagnosis of CF or CFTR-related disease and either: 1) evidence for a partial function mutation not currently covered or likely to be covered for treatment with a CFTR modulator (Substudy 1), or 2) N1303K CFTR and a minimal function mutation (Substudy 2)
• Sweat Chloride \< 80 mmol/L and/or pancreatic sufficiency (no exogenous pancreatic enzyme supplement therapy) or carrying the N1303K CFTR variant
• Able to perform spirometry meeting American Thoracic Society (ATS) criteria for acceptability and repeatability
• Clinically stable in the past 4 weeks with no evidence of CF exacerbation (prior to screening and study Day 1)
• Willingness to use at least one form of acceptable birth control including abstinence or condom with spermicide. This will include birth control for at least one month prior to screening and agreement to use such a method during study participation for an additional four weeks after the last administration of study drug
• Ability to take Trikafta
• Agreement to adhere to all current medical therapies as designated by the CF care center physician

You may not qualify if:

• Documented history of drug or alcohol abuse within the last year
• Subjects should not have a pulmonary exacerbation or changes in therapy for pulmonary disease in the 4 weeks prior to screening
• Listed for lung or liver transplant at the time of screening
• Cirrhosis or elevated liver transaminases \> 3 times the upper limit of normal
• Pregnant or breastfeeding
• Inhibitors or inducers of CYP3A4, including certain herbal medications and grapefruit/grapefruit juice, or other medicines known to negatively influence Trikafta administration
• History of solid organ transplant
• Active therapy for non-tuberculosis mycobacterial infection or any plan to initiate non-tuberculosis mycobacterial therapies during the study period
• Known allergy to Trikafta
• Treatment in the last 6 months with an approved CFTR modulator
• Any other condition that in the opinion of the lead investigators might confound results of the study or pose an additional risk from administering study drug
• Treatment with another investigational drug or other intervention within one month prior to enrollment, throughout the duration of study participation, and for an additional four weeks following final drug administration
• Evidence of cataract/lens opacity determined to be clinically significant by an ophthalmologist at or within 3 months prior to the Screening Visit

Sponsors & Collaborators

• Emory University: lead
• National Heart, Lung, and Blood Institute (NHLBI): collaborator
• Cystic Fibrosis Foundation: collaborator
• The University of Texas Health Science Center, Houston: collaborator

Study Sites (2)

University of Alabama Cystic Fibrosis Research Center

Birmingham, Alabama, 35233, United States

Location

Emory Children's Center

Atlanta, Georgia, 30322, United States

Location

Related Publications (1)

• Solomon GM, Linnemann RW, Rich R, Streby A, Buehler B, Hunter E, Vijaykumar K, Hunt WR, Brewington JJ, Rab A, Bai SP, Westbrook AL, McNicholas-Bevensee C, Hong J, Manfredi C, Barilla C, Suzuki S, Davis BR, Sorscher EJ. Evaluation of elexacaftor-tezacaftor-ivacaftor treatment in individuals with cystic fibrosis and CFTRN1303K in the USA: a prospective, multicentre, open-label, single-arm trial. Lancet Respir Med. 2024 Dec;12(12):947-957. doi: 10.1016/S2213-2600(24)00205-4. Epub 2024 Aug 26.

  PMID: 39208836 RESULT

MeSH Terms

Conditions

Cystic Fibrosis

Interventions

elexacaftor, ivacaftor, tezacaftor drug combination; ivacaftor; tezacaftor; elexacaftor

Condition Hierarchy (Ancestors)

Pancreatic Diseases; Digestive System Diseases; Lung Diseases; Respiratory Tract Diseases; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Infant, Newborn, Diseases

Results Point of Contact

• Title: Eric Sorscher, MD
• Organization: Emory University

esorscher@emory.edu

205-612-1327

Study Officials

• Eric Sorscher, MD

  Emory University

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: April 13, 2018
• First Posted: April 23, 2018
• Study Start: September 4, 2019
• Primary Completion: February 13, 2024
• Study Completion: February 13, 2024
• Last Updated: September 11, 2025
• Results First Posted: September 11, 2025

Record last verified: 2025-08

Data Sharing

• IPD Sharing: Will not share

Locations

US (2)